Department of Pharmacy, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA.
Department of Neurology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA.
J Immunother Cancer. 2017 Dec 19;5(1):99. doi: 10.1186/s40425-017-0302-x.
Programmed cell death ligand-1 (PD-L1) expression has been reported in up to 61% of high grade gliomas (HGG). The purpose of this study was to describe safety and efficacy of PD-1 inhibition in patients with refractory HGGs.
This Institutional Review Board approved single center retrospective study included adult patients with pathologically confirmed HGG who received a PD-1 inhibitor from 9/2014-10/2016 outside of a clinical trial at Memorial Sloan Kettering Cancer Center.
Twenty five HGG patients received pembrolizumab as part of a compassionate use program. Median age was 50 years (range 30-72); 44% were men; 13 had glioblastoma (52%), 7 anaplastic astrocytoma (28%), 2 anaplastic oligodendroglioma (8%), 2 unspecified HGG (8%), and 1 gliosarcoma (4%). Median prior lines of treatments were 4 (range 1-9). Nineteen (76%) previously failed bevacizumab. Median KPS was 80 (range 50-100). Concurrent treatment included bevacizumab in 17 (68%) or bevacizumab and temozolomide in 2 (8%) patients. Median number of doses administered was 3 (range 1-14). Outcomes were assessed in 24 patients. PD-1 inhibitor related adverse events included LFT elevations, hypothyroidism, diarrhea, myalgias/arthralgias, and rash. Best radiographic response was partial response (n = 2), stable disease (n = 5), and progressive disease (n = 17). Median progression free survival (PFS) was 1.4 months (range 0.2-9.4) and median overall survival (OS) was 4 months (range 0.5-13.8). Three-month PFS was 12% and 6-month OS was 28%.
While response rates are low, a few patients had a prolonged PFS. Pembrolizumab was tolerated with few serious toxicities, even in patients receiving concomitant therapy.
程序性死亡配体 1（PD-L1）的表达在高达 61%的高级别神经胶质瘤（HGG）中被报道。本研究的目的是描述在难治性 HGG 患者中 PD-1 抑制的安全性和疗效。
这项经机构审查委员会批准的单中心回顾性研究纳入了在 Memorial Sloan Kettering 癌症中心接受临床试验之外的 PD-1 抑制剂治疗的病理证实为 HGG 的成年患者。
25 名 HGG 患者接受了 pembrolizumab 作为同情使用计划的一部分。中位年龄为 50 岁（范围 30-72）；44%为男性；13 例为胶质母细胞瘤（52%），7 例为间变性星形细胞瘤（28%），2 例为间变性少突胶质细胞瘤（8%），2 例为未特指的 HGG（8%），1 例为胶质肉瘤（4%）。中位既往治疗线数为 4 条（范围 1-9）。19 例（76%）患者既往曾接受贝伐珠单抗治疗失败。中位 KPS 为 80（范围 50-100）。同时治疗包括 17 例（68%）贝伐珠单抗或 2 例（8%）贝伐珠单抗和替莫唑胺。中位给药剂量为 3（范围 1-14）。24 例患者评估了治疗结果。PD-1 抑制剂相关不良事件包括 LFT 升高、甲状腺功能减退、腹泻、肌痛/关节痛和皮疹。最佳影像学反应为部分缓解（n=2）、疾病稳定（n=5）和疾病进展（n=17）。中位无进展生存期（PFS）为 1.4 个月（范围 0.2-9.4），中位总生存期（OS）为 4 个月（范围 0.5-13.8）。3 个月的 PFS 为 12%，6 个月的 OS 为 28%。
虽然反应率较低，但少数患者的 PFS 延长。Pembrolizumab 耐受性良好，即使在同时接受治疗的患者中，也很少出现严重毒性。
